[Effects on bone mass of oral alendronate, hormone replacement therapy and combined regimes in post-menopausal women: preliminary report on a comparative study].
The results of a prospective study that compared the short term effects on skeletal bone of oral alendronate, transdermal hormone replacement therapy (HRT) and two combined regimens with both medications are reported. Ninety six posmenopausal women with osteopenia (WHO classification) in lumbar spine or femoral neck measured by DEXA (table 1) were included in 4 therapeutic groups: Group I (n:19): 17 beta-Estradiol 50 micrograms daily transdermally/medroxiprogesterone 2.5 mg orally per day; Group II (n:42): alendronate 10 mg/day orally; Group III (n:15): HRT + alendronate 10 mg/day and Group IV (n:20): HTR + alendronate 5 mg/day. After 12 month treatment, lumbar bone mineral density (BMD) significantly increased to 3.6%; 4.1%; 6.5% y 3.1% in group I to IV, respectively (p < 0.01; figure 1). Differences among groups do not reached statistical significance. The percentage of responders to medication in each group was of 68.8%; 92%; 90% y 83%, respectively. Bone mineral density in femoral neck (FN) increased with all regimens, though mean values did not surpass method variation coefficient. Differences from baseline were statistically significant in group I (p < 0.05). The percentage of responders in this region was 58.8%; 60%; 62.5% y 45.5%, respectively. Biochemical bone markers (table 2), especially urinary pyridinoline and serum osteocalcin, showed a trend in bone metabolism inhibition that was more sustained in group III, as show mainly by the bone markers pyridinolines and osteocalcin. It is concluded that either single therapy with alendronate or estrogen or their combination halted bone loss in most patients leading to bone mass gain mainly in lumbar spine in the short term. However, bone effects with hormone replacement therapy in association with alendronate 10 mg were comparatively major, indicating the potential benefits of this regimen in the long term.


Numerical transforms.
Numerical computation of transforms is now widely practiced in science and industry and has been revolutionized by the development of fast transforms that make feasible computing projects that once could not be contemplated. The article discusses the significance of transforms in numerical work, defines the modern forms of several common transforms and their inverses, gives examples, and describes and gives references to methods of numerical evaluation.


Harmonic segregation through mistuning can improve fundamental frequency discrimination.
This study investigated the relationship between harmonic frequency resolution and fundamental frequency (f(0)) discrimination. Consistent with earlier studies, f(0) discrimination of a diotic bandpass-filtered harmonic complex deteriorated sharply as the f(0) decreased to the point where only harmonics above the tenth were presented. However, when the odd harmonics were mistuned by 3%, performance improved dramatically, such that performance nearly equaled that found with only even harmonics present. Mistuning also improved performance when alternating harmonics were presented to opposite ears (dichotic condition). In a task involving frequency discrimination of individual harmonics within the complexes, mistuning the odd harmonics yielded no significant improvement in the resolution of individual harmonics. Pitch matches to the mistuned complexes suggested that the even harmonics dominated the pitch for f(0)'s at which a benefit of mistuning was observed. The results suggest that f(0) discrimination performance can benefit from perceptual segregation based on inharmonicity, and that poor performance when only high-numbered harmonics are present is not due to limited peripheral harmonic resolvability. Taken together with earlier results, the findings suggest that f(0) discrimination may depend on auditory filter bandwidths, but that spectral resolution of individual harmonics is neither necessary nor sufficient for accurate f(0) discrimination.


Successful Treatment of Persistent Coronavirus Disease 2019 Infection in a Patient With Hypogammaglobulinemia With REGN-COV2: A Case Report.
A 55-year-old man with hypogammaglobulinemia due to previous rituximab treatment developed persistent coronavirus disease 2019 pneumonia. Treatment with REGN-COV2 (casirivimab and imdevimab) resulted in the clearance of the infection. Targeted antiviral antibodies may be an important weapon in the management of immunocompromised patients infected with severe acute respiratory syndrome coronavirus 2 who fail to mount an immune response.


Gene expression study in monocytes: evidence of inflammatory dysregulation in early-onset obsessive-compulsive disorder.
Obsessive-compulsive disorder (OCD) has a complex etiology that seems to include immune dysfunction and alterations in circulating monocytes. To investigate the immune basis and the functional dysregulation of monocytes in this disease, we analyzed gene expression in the peripheral monocytes of pediatric patients with OCD (N = 102) compared to controls (N = 47). We examined gene expression in primary cultures of peripheral monocytes from participants, under basal conditions and under exposure to lipopolysaccharide (LPS) to stimulate immune response. Whole-genome expression was assessed in 8 patients and 8 controls. Differentially expressed genes were identified followed by protein-protein interaction network construction and functional annotation analysis to identify the genes and biological processes that are altered in the monocytes of OCD patients. We also explored the expression levels of selected genes in monocytes from the other participants using qPCR. Several changes in gene expression were observed in the monocytes of OCD patients, with several immune processes involved under basal conditions (antigen processing and presentation, regulation of immune system and leukocyte cell adhesion) and after LPS stimulation (immune and inflammatory response, cytokine production and leukocyte activation). Despite the qPCR analysis provided no significant differences between patients and controls, high correlations were observed between the expression levels of some of the genes and inflammatory markers (i.e., T helper 17 and regulatory T cell levels, total monocyte and proinflammatory monocyte subset levels, and the cytokine production by resting and stimulated monocytes) of the study participants. Our findings provide more evidence of the involvement of monocyte dysregulation in early-onset OCD, indicating a proinflammatory predisposition and an enhanced immune response to environmental triggers.


DN1(p) circadian neurons coordinate acute light and PDF inputs to produce robust daily behavior in Drosophila.
Daily behaviors in animals are determined by the interplay between internal timing signals from circadian clocks and environmental stimuli such as light. How these signals are integrated to produce timely and adaptive behavior is unclear. The fruit fly Drosophila exhibits clock-driven activity increases that anticipate dawn and dusk and free-running rhythms under constant conditions. Flies also respond to the onset of light and dark with acute increases in activity. Mutants of a novel ion channel, narrow abdomen (na), lack a robust increase in activity in response to light and show reduced anticipatory behavior and free-running rhythms, providing a genetic link between photic responses and circadian clock function. We used tissue-specific rescue of na to demonstrate a role for approximately 16-20 circadian pacemaker neurons, a subset of the posterior dorsal neurons 1 (DN1(p)s), in mediating the acute response to the onset of light as well as morning anticipatory behavior. Circadian pacemaker neurons expressing the neuropeptide PIGMENT-DISPERSING FACTOR (PDF) are especially important for morning anticipation and free-running rhythms and send projections to the DN1(p)s. We also demonstrate that DN1(p)Pdfr expression is sufficient to rescue, at least partially, Pdfr morning anticipation defects as well as defects in free-running rhythms, including those in DN1 molecular clocks. Additionally, these DN1 clocks in wild-type flies are more strongly reset to timing changes in PDF clocks than other pacemaker neurons, suggesting that they are direct targets. Taking these results together, we demonstrate that the DN1(p)s lie at the nexus of PDF and photic signaling to produce appropriate daily behavior.


Clinic Factors Associated With Mailed Fecal Immunochemical Test (FIT) Completion: The Difference-Making Role of Support Staff.
Mailed fecal immunochemical test (FIT) programs can facilitate colorectal cancer (CRC) screening. We sought to identify modifiable, clinic-level factors that distinguish primary care clinics with higher vs lower FIT completion rates in response to a centralized mailed FIT program. We used baseline observational data from 15 clinics within a single urban federally qualified health center participating in a pragmatic trial to optimize a mailed FIT program. Clinic-level data included interviews with leadership using a guide informed by the Consolidated Framework for Implementation Research (CFIR) and FIT completion rates. We used template analysis to identify explanatory factors and configurational comparative methods to identify specific combinations of clinic-level conditions that uniquely distinguished clinics with higher and lower FIT completion rates. We interviewed 39 clinic leaders and identified 58 potential explanatory factors representing clinic workflows and the CFIR inner setting domain. Clinic-level FIT completion rates ranged from 30% to 56%. The configurational model for clinics with higher rates (≥37%) featured any 1 of the following 3 factors related to support staff: (1) adding back- or front-office staff in past 12 months, (2) having staff help patients resolve barriers to CRC screening, and (3) having staff hand out FITs/educate patients. The model for clinics with lower rates involved the combined absence of these same 3 factors. Three factors related to support staff differentiated clinics with higher and lower FIT completion rates. Adding nonphysician support staff and having those staff provide enabling services might help clinics optimize mailed FIT screening programs.


[Cytotoxic effect of antineoplastic substances and their effect on DNA synthesis and cGMP level in tumor and normal tissues].
The cytostatic effect of antitumour agents line on the level of malignantly changed actively proliferating system (tumour growth) and normal actively proliferating system (splin) was investigated on the basis of DNA synthesis and cGMP rate. Studies of these antitumour agents were carried out on three tumour growth models (Pliss lymphosarcoma, Yablonovskaya glyoblastoma and human glyoblastoma heterografts (subcapsular test). It has been demonstrated that chlofiden, brotheophine, vincristine, adriablastine, natulan, phthorafur have a marked and stable effect of DNA synthesis inhibition, resulting in their marked cytostatic effect and antitumour action stability under the therapy conditions. The experimental data have shown cGMP rates decrease in Pliss lymphosarcoma in the case of high antitumour activity.


Elucidating the microbial ecological mechanisms on the electro-fermentation of caproate production from acetate via ethanol-driven chain elongation.
Electro-fermentation (EF) is an attractive way to implement the chain elongation (CE) process, by controlling the fermentation environment and reducing the dosage of external electron donors (EDs). However, besides the coexistence performance of external EDs and electrode, applications of EF technology on the fermentation broth containing both EDs and electron acceptors during CE process, are all still limited. The current study investigated the contribution of EF to caproate production, under different acetate: ethanol ratios (RA/E). The effect of multiple EDs, both from ethanol and the bio-cathode, on caproate production, was also assessed. A proof-of-concept, based on experimental data, was presented for the EF-mediated ethanol-driven CE process. Experimental results showed that ethanol, together with the additional electron donors from the bio-cathode, was beneficial for the stable caproate production. The caproate concentration increased with the decrease of RA/E, while the bio-cathode further contributed to 10.7%-26.1 % increase of caproate concentration. Meanwhile, the hydrogen partial pressure tended to 0.10 ± 0.01 bar in all controlled EF reactors, thus favoring caproate production. This was attributed to the increased availability EDs, i.e., hydrogen and ethanol, generated by the electrode and electrochemically active bacteria (EAB), which might create multiple additional pathways to achieve caproate production. Molecular ecological networks analysis of the key microbiomes further revealed underlying cooperative relationships, beneficial to the chain elongation process. The genus Clostridium_sensu_stricto, as the dominant microbial community, was positively related to acetogens, EAB and fermenters.


Clinical outcomes of magnetic activated sperm sorting in infertile men candidate for ICSI.
Magnetic activated cell sorting (MACS) with annexin V microbeads deselected apoptotic sperm with externalized phosphatidylserine (PS) residues on their surface and decrease chance of such sperm to be inseminated. Therefore, the aim of this study was to evaluate efficiency of MACS procedure in a prospective randomized trial. Sixty-two semen samples were allocated into two groups and processed according to: (i) a combination of MACS with density gradient centrifugation (MACS-DGC) as study group (N = 29); and (ii) DGC alone as a control group (N = 33). Fertilization, embryo quality, pregnancy and implantation rates were compared between the two groups. Although, no significant difference was observed in fertilization rates between the two groups, the percentage of high-quality embryos, pregnancy and implantation rates was significantly higher in the MACS-DGC group compared to DGC alone. Therefore, MACS may help to select the most fertile sperm and improve clinical outcomes of intra-cytoplasmic sperm injection (ICSI).


Sequential activation of different pathway networks in ischemia-affected and non-affected myocardium, inducing intrinsic remote conditioning to prevent left ventricular remodeling.
We have analyzed the pathway networks of ischemia-affected and remote myocardial areas after repetitive ischemia/reperfusion (r-I/R) injury without ensuing myocardial infarction (MI) to elaborate a spatial- and chronologic model of cardioprotective gene networks to prevent left ventricular (LV) adverse remodeling. Domestic pigs underwent three cycles of 10/10 min r-I/R by percutaneous intracoronary balloon inflation/deflation in the mid left anterior descending artery, without consecutive MI. Sham interventions (n = 8) served as controls. Hearts were explanted at 5 h (n = 6) and 24 h (n = 6), and transcriptomic profiling of the distal (ischemia-affected) and proximal (non-affected) anterior myocardial regions were analyzed by next generation sequencing (NGS) and post-processing with signaling pathway impact and pathway network analyses. In ischemic region, r-I/R induced early activation of Ca-, adipocytokine and insulin signaling pathways with key regulator STAT3, which was also upregulated in the remote areas together with clusterin (CLU) and TNF-alpha. During the late phase of cardioprotection, antigen immunomodulatory pathways were activated with upregulation of STAT1 and CASP3 and downregulation of neprilysin in both zones, suggesting r-I/R induced intrinsic remote conditioning. The temporo-spatially differently activated pathways revealed a global myocardial response, and neprilysin and the STAT family as key regulators of intrinsic remote conditioning for prevention of adverse remodeling.


Before It Gets Started: Regulating Translation at the 5' UTR.
Translation regulation plays important roles in both normal physiological conditions and diseases states. This regulation requires cis-regulatory elements located mostly in 5' and 3' UTRs and trans-regulatory factors (e.g., RNA binding proteins (RBPs)) which recognize specific RNA features and interact with the translation machinery to modulate its activity. In this paper, we discuss important aspects of 5' UTR-mediated regulation by providing an overview of the characteristics and the function of the main elements present in this region, like uORF (upstream open reading frame), secondary structures, and RBPs binding motifs and different mechanisms of translation regulation and the impact they have on gene expression and human health when deregulated.


Slow water dynamics in dehydrated human Jurkat T cells evaluated by dielectric spectroscopy with the Bruggeman-Hanai equation.
The picosecond orientational dynamics of intracellular water was measured by dielectric spectroscopy, with the aim of revealing the effects of cryoprotective agents (CPAs) on biological cells. As a first step, Jurkat cells (human T lymphocyte cells) suspended in aqueous sucrose solutions of different concentrations ranging from 0.3 M (isotonic) to 0.9 M (hypertonic) were examined at 25 °C with a frequency range up to 43.5 GHz. The Bruggeman-Hanai equation was employed to obtain a cellular dielectric spectrum without extracellular contributions from the measured complex permittivity of the cell suspensions. By analyzing the γ process around 1010 Hz based on the Debye relaxation function, two types of water (bulk-like water and hydration water with slower molecular dynamics) were observed. An increase in the fraction of intracellular slower water was observed in the dehydrated cells which had a highly concentrated environment of biomolecules.


A Retrospective Analysis of the Effectiveness of the Longevity Protocol for Assessing the Risk of Implant Failure.
A new, computerized diagnostic tool, called the Longevity Protocol, was recently developed to predict implant failure. The present retrospective analysis was undertaken to assess the prognostic validity of this protocol. A selected group of patients who had been treated with implants over the past 10 years at six dental clinics and experienced implant failure were included in the analysis. Another group of patients with similar characteristics, not experiencing implant failure, was used as control. In April of 2015, data about each of the patients was entered into the Longevity Protocol database. For each patient, the risk assessment produced by the protocol was compared to whether the implants eventually failed. The implant failure predictions and actual implant failures were compared. The Longevity Protocol analyzed the possible failure of 595 implants placed in 221 patients (323 implants placed in 138 patients classified as low risk, 180 implants placed in 55 patients classified as moderate risk, and 92 implants placed in 28 patients classified as high risk). The actual percentage of implant failure in the three groups was 10%, 15%, and 22%, respectively. The differences between the groups were statistically significant. The sensitivity and specificity of the Longevity Protocol was 84.9% and 11.90% in the high/moderate risk group and 47.17% and 32.74% in the low risk group, respectively. Statistically significant results were obtained. The Longevity Protocol reliably identified patients who risked implant failure. The protocol appears to be an important tool for prognosis assessment.


A new hemizygous missense mutation, c.454T>C (p.S152P), in AKAP4 gene is associated with asthenozoospermia.
Asthenozoospermia (ASZ) is a condition characterized by reduced forward motility of spermatozoa affecting approximately 19% of infertile men. A kinase anchor protein 4 (AKAP4) is an X-linked testis-specific gene and plays a major role in sperm motility and flagella formation. However, few studies have reported its association with ASZ. Here, we sequenced for exonic mutations of human AKAP4 gene by high-fidelity PCR/Sanger sequencing in peripheral blood samples from 150 ASZ patients and 150 fertile men. We reported the identification of three novel hemizygous mutations unique to four ASZ patients, including one patient carrying missense mutation c.454T>C (p.S152P), two patient carrying synonymous mutation c.1173T>C (p.H391H), and one patient carrying synonymous mutation c.2007 A>G (p.R669R). The p.S152P mutation was located in a precursor pro-polypeptide domain of AKAP4 protein, which was predicted to be damaging by SIFT and PolyPhen-2 and could cause the protein accumulation in the cytoplasm of COS-7 cells. The mature protein of AKAP4 was absent in spermatozoa of ASZ patient harboring AKAP4 p.S152P mutation. Further in vitro cellular assays showed that reactive oxygen species (ROS), malondialdehyde (MDA), myeloperoxidase (MPO) levels, and apoptotic cells were increased in GC2-spd cells by AKAP4 p.S152P mutant protein, whereas superoxide dismutase (SOD) level was decreased. AKAP4 p.H391H and p.R669R mutant proteins were coimmunoprecipitated with ribonuclease T2 (RNASET2) protein in GC2-spd cells, whereas no interaction between the AKAP4 p.S152P mutant protein and RNASET2 protein was observed. In addition, AKAP4 p.S152P mutant protein could decrease the activity of PKA/PI3K signaling. Overall, our study identifies a novel AKAP4 p.S152P mutation is associated with ASZ probably through affecting oxidative stress and cell apoptosis by regulating the interaction with RNASET2 and the activity of the PKA/PI3K signaling pathway.


Autologous humoral response to human gliomas and analysis of certain cell surface antigens: in vitro study with the use of microcytotoxicity and immune adherence assays.
In 25 patients with intracranial gliomas, the autologous humoral response was studied in vitro with the use of microcytotoxicity (MC) and immune adherence (IA) assays. Antibodies were detected to autologous cultures in 44% of the cases by MC and in 50% by IA. These positive responses occurred in statistically different groups of patients, which suggested that different functional types of antibody were involved. Direct testing and absorption experiments showed that antibody was not significantly directed against autologous fibroblasts. Autologous cytotoxic antibodies were detected by 67% of astrocytoma cases and in only 10% of patients harboring a glioblastoma, the most anaplastic tumor of the glioma series. By means of the IA assay, absorption experiments were performed with the use of adult and fetal brains and cultures of autologous and allogeneic gliomas and fibroblasts. In this serologic system, the types of antigenic expression of a human glioma could be categorized as follows: 1) highly restricted glioma antigen(s), 2) common glioma antigen(s), 3) neurectoderm-derived antigen(s), and 4) brain and fibroblast-associated oncofetal antigen(s). The common glioma antigen and oncofetal antigen appeared to be qualitatively different, and the glioma antigen was expressed in uncultured tumor tissue.


Cholangiocarcinoma: a compact review of the literature.
Cholangiocarcinoma (CC) is a devastating cancer arising from biliary epithelia. Unfortunately, the incidence of this disease is increasing in Western countries. These tumors progress insidiously, and liver failure, biliary sepsis, malnutrition and cancer cachexia are general modes of death associated with this disease. To date, no established therapy for advanced disease has been established or validated. However, our knowledge in tumor biology is increasing dramatically and new drugs are under investigation for treatment of this notorious tumor. In clinical practice, there are better diagnostic tools in use to facilitate an earlier diagnosis of CC, at least in those patients with known risk factors. CC is resectable for cure in only a small percentage of patients. Preoperative staging for vascular and biliary extension of CC is very important in this tumor. Laparoscopy and recently endosonography seem to protect against unnecessary laparotomies in these patients. During the last 15 years, aggressive surgical approaches, including combined liver resections and vascular reconstructive surgical expertise, have improved survival in patients with CC. Surgery is contraindicated in CC cases having primary sclerosing cholangitis (PSC). Although CC was previously considered a contraindication to liver transplantation, new cautious protocols, including neo-adjuvant chemoradiation therapies and staging procedures before the transplantation, have made it possible to achieve long-term survival after liver transplantation in this disease. New ablative therapies with photodynamic therapy, intraductal high-intensity ultrasonography and chemotherapy-impregnated plastic biliary endoprosthesis are important steps in the palliative management of extra-hepatic CCs. Radiofrequency and chemo-embolization methods are also applicable for intra-hepatic CCs as palliative modes of treatment. We need more prospective randomized controlled trials to evaluate the role of the new emerging therapies for CC patients.


Maculosin, a non-toxic antioxidant compound isolated from Streptomyces sp. KTM18.
Streptomyces species are prolific sources of bioactive secondary metabolites known especially for their antimicrobial and anticancer activities. This study sought to isolate and characterize antioxidant molecules biosynthesized by Streptomyces sp. KTM18. The antioxidant potential of an isolated compound and its toxicity were accessed. The compound was purified using bioassay-guided chromatography techniques. Nuclear magnetic resonance (NMR) experiments were carried out for structure elucidation. The antioxidant potential of the isolated compound was determined using DPPH free radical scavenging assay. The toxicity of the isolated compound was measured using a brine shrimp lethality (BSL) assay. Ethyl acetate extract of Streptomyces sp. KTM18 showed more than 90% inhibition of DPPH free radical at 50 µg/mL of the test concentration. These data were the strongest among 13 Streptomyces isolates (KTM12-KTM24). The active molecule was isolated and characterized as maculosin (molecular formula, C14H16N2O3 as determined by the [M + H]+ peak at 261.1259). The DPPH free radical scavenging activity of pure maculosin was higher (IC50, 2.16 ± 0.05 µg/mL) than that of commercial butylated hydroxyanisole (BHA) (IC50, 4.8 ± 0.05 µg/mL). No toxicity was observed for maculosin (LD50, <128 µg/mL) in brine shrimp lethality assay (BSLA) up to the compound's antioxidant activity (IC50) concentration range. The commercial standard, berberine chloride, showed toxicity in BSLA with an LD50 value of 8.63 ± 0.15 µg/mL. Maculosin may be a leading drug candidate in various cosmetic and therapeutic applications owing to its strong antioxidant and non-toxic properties.


Could MRI Be Used To Image Kidney Fibrosis? A Review of Recent Advances and Remaining Barriers.
A key contributor to the progression of nearly all forms of CKD is fibrosis, a largely irreversible process that drives further kidney injury. Despite its importance, clinicians currently have no means of noninvasively assessing renal scar, and thus have historically relied on percutaneous renal biopsy to assess fibrotic burden. Although helpful in the initial diagnostic assessment, renal biopsy remains an imperfect test for fibrosis measurement, limited not only by its invasiveness, but also, because of the small amounts of tissue analyzed, its susceptibility to sampling bias. These concerns have limited not only the prognostic utility of biopsy analysis and its ability to guide therapeutic decisions, but also the clinical translation of experimental antifibrotic agents. Recent advances in imaging technology have raised the exciting possibility of magnetic resonance imaging (MRI)-based renal scar analysis, by capitalizing on the differing physical features of fibrotic and nonfibrotic tissue. In this review, we describe two key fibrosis-induced pathologic changes (capillary loss and kidney stiffening) that can be imaged by MRI techniques, and the potential for these new MRI-based technologies to noninvasively image renal scar.


Serum concentrations and subcutaneous adipose tissue mRNA expression of omentin in morbid obesity and type 2 diabetes mellitus: the effect of very-low-calorie diet, physical activity and laparoscopic sleeve gastrectomy.
Omentin is a novel adipokine with insulin-sensitizing effects expressed predominantly in visceral fat. We investigated serum omentin levels and its mRNA expression in subcutaneous adipose tissue (SCAT) of 11 women with type 2 diabetes mellitus (T2DM), 37 obese non-diabetic women (OB) and 26 healthy lean women (C) before and after various weight loss interventions: 2-week very-low-calorie diet (VLCD), 3-month regular exercise and laparoscopic sleeve gastrectomy (LSG). At baseline, both T2DM and OB groups had decreased serum omentin concentrations compared with C group while omentin mRNA expression in SCAT did not significantly differ among the groups. Neither VLCD nor exercise significantly affected serum omentin concentrations and its mRNA expression in SCAT of OB or T2DM group. LSG significantly increased serum omentin levels in OB group. In contrast, omentin mRNA expression in SCAT was significantly reduced after LSG. Baseline fasting serum omentin levels in a combined group of the studied subjects (C, OB, T2DM) negatively correlated with BMI, CRP, insulin, LDL-cholesterol, triglycerides and leptin and were positively related to HDL-cholesterol. Reduced circulating omentin levels could play a role in the etiopathogenesis of obesity and T2DM. The increase in circulating omentin levels and the decrease in omentin mRNA expression in SCAT of obese women after LSG might contribute to surgery-induced metabolic improvements and sustained reduction of body weight.


PART I: FIGHTING CANCER WITH DEADLY BACTERIA.
A 200-year-old observation might provide a new way to eliminate tumors by infecting cancer patients with bacteria. Kristie Nybo explores a new approach that could transform cancer treatment.


Clarithromycin suppresses lipopolysaccharide-induced interleukin-8 production by human monocytes through AP-1 and NF-kappa B transcription factors.
Erythromycin and other macrolides are effective for the treatment of chronic inflammatory airway diseases such as diffuse panbronchiolitis (DPB) and chronic sinusitis. The effect of macrolides in DPB is suggested to be anti-inflammatory rather than antibacterial. We investigated the effects of clarithromycin on interleukin-8 (IL-8) production using human peripheral monocytes and the human monocytic leukaemia cell line, THP-1. Bacterial extracts from Escherichia coli, Pseudomonas aeruginosa and Helicobacter pylori, as well as E. coli-derived lipopolysaccharide (LPS), induced IL-8 production. Clarithromycin suppressed this production in a dose-dependent manner in both monocytes and THP-1 cells (49.3-75.0% inhibition at 10 mg/L). A luciferase reporter gene assay with plasmids containing a serially deleted IL-8 promoter fragment showed that both the activator protein-1 (AP-1) and/or the nuclear factor-kappa B (NF-kapp aB) binding sequences were responsible for the LPS and clarithromycin responsiveness of the IL-8 promoter. Consistently, in an electromobility shift assay, LPS increased the specific binding of both AP-1 and NF-kappaB, whereas clarithromycin suppressed it. Moreover, LPS and clarithromycin regulated three other promoters that have either the NF-kappa B or the AP-1 binding sequences: two synthetic (pAP-1-Luc and pNF-kappa B-Luc) and one naturally occurring (ELAM-Luc). Our results indicate that clarithromycin modified inflammation by sup-pressing IL-8 production and that clarithromycin may affect the expression of other genes through AP-1 and NF-kappa B. In addition to treatment of airway diseases, the anti-inflammatory effect of macrolides may be beneficial for the treatment of other inflammatory diseases such as chronic gastritis caused by H. pylori.


Recurrent thrombocytopenic purpura associated with accessory spleen.
In the case of a boy with a relapsed thrombocytopenic purpura removal of a splenunculus, shown by radioisotope scanning, resulted in a partial remission. The significance of the association of relapse in ITP and the presence of splenunculi remains unknown: investigation of similar cases would clarify the matter.


Phorbol ester induces differentiation of a human prostatic cancer cell line TSU-Pr1 into cells with characteristics of microglia.
The effects of various reagents on the induction of differentiation of the human prostatic cancer cell line, TSU-Pr1, were examined. Among these agents, the phorbol ester, TPA, almost completely suppressed cell proliferation at the concentration of 10(-8) M, and induced remarkable morphologic changes yielding cells with the microglial feature of an ameboid and/or ramified shape. More than 90% of the cells underwent the induction of morphologic changes by day 7 after treatment with 10(-8) M TPA. The expression of reliable microglial markers, alpha-naphthyl acetate esterase activity and CD11b, was observed in the differentiated cells. The data presented here suggest that TPA induces differentiation of a human prostate cancer cell line into cells with the characteristics of microglia.


Association of peroxisome proliferator-activated receptor delta and additional gene-smoking interaction on cardiovascular disease.
To investigate the impact of peroxisome proliferator-activator receptor delta (PPARD) gene polymorphism and additional gene-smoking interaction on cardiovascular disease (CVD) risk based on this Chinese population. A total of 1048 subjects (617 males, 431 females) with a mean age of 52.9 ± 14.1 years old were selected, including 520 CVD patients and 528 normal control subjects. The logistic regression model was used to examine the association between three SNPs and CVD risk, odds ratio (OR), and 95% confident interval (95%CI) were calculated. Generalized multifactor dimensionality reduction (GMDR) was employed to investigate the gene-smoking interaction. Genotypes of variants in rs2016520 and rs9794 were associated with decreased CVD risk, and CVD risk was significantly lower in carriers of C allele of the rs2016520 polymorphism than those with the TT genotype (TC+CC versus TT), adjusted OR (95%CI) = 0.71 (0.56-0.86). In addition, we also found that CVD risk was also significantly lower in carriers of the G allele of the rs9794 polymorphism than those with the CC genotype (CG+ GG versus CC), adjusted OR (95%CI) = 0.69 (0.53-0.86). GMDR analysis suggested a potential gene-environment interaction between rs2016520 and smoking. Overall, the two-locus models had a cross-validation consistency of 10 of 10, and had the testing accuracy of 62.17%, and never smokers with TC or CC of the rs2016520 genotype have the lowest CVD risk, compared to smokers with TT of rs2016520, OR (95%CI) was 0.42 (0.23-0.66). The minor allele of rs2016520 and rs9794 in PPAR-δ and interaction between rs2016520 and non-smoking were associated with decreased risk of CVD.


Generalized Zero-Shot Cross-Modal Retrieval.
Cross-modal retrieval is an important research area due to its wide range of applications, and several algorithms have been proposed to address this task. We feel that it is the right time to take a step back and analyze the current status of research in this area. As new object classes are continuously being discovered over time, it is necessary to design algorithms that can generalize to data from previously unseen classes. Towards that goal, our first contribution is to establish protocols for generalized zero-shot cross-modal retrieval and analyze the generalization ability of the standard cross-modal algorithms. Second, we propose a semantic-aware ranking algorithm that can be used as an add-on to any existing cross-modal approach to improve its performance on both seen and unseen classes. Finally, we propose a modification of the standard evaluation metric (MAP for single-label data and NDCG for multi-label data), which we feel is a more intuitive measure of the cross-modal retrieval performance. Extensive experiments on two single-label and three multi-label cross-modal datasets show the effectiveness of the proposed approach.


Using rehabilitation theory to teach medical-surgical nursing to undergraduate students.
Medical-surgical nursing has been taught at the undergraduate level using several approaches (Bocchi, Pessuto, & Dell'Aqua, 1996; Hinzman, 1996). Although a review of the literature indicates that nursing schools have had some success offering classes that focus on rehabilitation principles and theory, there is no literature about medical-surgical nursing that is taught from a rehabilitation perspective. This article describes an undergraduate medical-surgical nursing course that teaches students how to care for the chronically ill using rehabilitation theory and principles.


Will my patient fall?
Effective multifactorial interventions reduce the frequent falling rate of older patients by 30% to 40%. However, clinical consensus suggests reserving these interventions for high-risk patients. Limiting fall prevention programs to high-risk patients implies that clinicians must recognize features that predict future falls. To identify the prognostic value of risk factors for future falls among older patients. Search of MEDLINE (1966-September 2004), CINAHL (1982-September 2004), and authors' own files to identify prospective cohort studies of risk factors for falls that performed a multivariate analysis of such factors. Two reviewers independently determined inclusion of articles and assessed study quality. Disagreements were resolved by consensus. Included studies were those identifying the prognostic value of risk factors for future falls among community-dwelling persons 65 years and older. Clinically identifiable risk factors were identified across 6 domains: orthostatic hypotension, visual impairment, impairment of gait or balance, medication use, limitations in basic or instrumental activities of daily living, and cognitive impairment. Eighteen studies met inclusion criteria and provided a multivariate analysis including at least 1 of the risk factor domains. The estimated pretest probability of falling at least once in any given year for individuals 65 years and older was 27% (95% confidence interval, 19%-36%). Patients who have fallen in the past year are more likely to fall again [likelihood ratio range, 2.3-2.8]. The most consistent predictors of future falls are clinically detected abnormalities of gait or balance (likelihood ratio range, 1.7-2.4). Visual impairment, medication variables, decreased activities of daily living, and impaired cognition did not consistently predict falls across studies. Orthostatic hypotension did not predict falls after controlling for other factors. Screening for risk of falling during the clinical examination begins with determining if the patient has fallen in the past year. For patients who have not previously fallen, screening consists of an assessment of gait and balance. Patients who have fallen or who have a gait or balance problem are at higher risk of future falls.


Structural covariance in the human cortex.
The morphology of the human cortex varies remarkably across individuals, regardless of overall brain size. It is currently unclear whether related cortical regions covary in gray matter density, as a result of mutually trophic influences or common experience-related plasticity. We acquired a structural magnetic resonance imaging scan from 172 subjects and extracted the regional gray matter densities from 12 readily identifiable regions of interest involved in sensorimotor or higher-order cognitive functions. We then used these values to predict regional densities in the remaining areas of the cortex, using voxel-based morphometry. This revealed patterns of positive and negative covariance that provide insight into the topographical organization of multiple cortical regions. We report that the gray matter density of a region is a good predictor of the density of the homotopic region in the contralateral hemisphere, with the striking exception of primary visual cortex. Whereas some regions express patterns of regional covariance that are mirror symmetrical relative to the interhemispheric fissure, other regions express asymmetric patterns of regional covariance. Finally, patterns of covariance are remarkably consistent between males and females, with the exception of the left amygdala, which is positively associated with the left and right anterior inferior temporal cortex in males and with the right angular gyrus in females. Our study establishes that the density of different cortical regions is coordinated within an individual. The coordinated variations we report are likely to be determined by both genetic and environmental factors and may be the basis for differences in individual behavior.


Healthy women with persistently elevated hCG levels: a case series of fourteen women.
To review our own data and that in the literature in order to assess likely morbidity and mortality risks and enhance the information that we can provide to patients suffering with this condition. This was a retrospective case series using data from the Sheffield Trophoblastic Disease Centre Database combined with data from prior publications. A diagnosis of elevated human chorionic gonadotropin (hCG) in an otherwise healthy woman carries an 11-19% risk of malignancy and 1-3% risk of mortality. Irrespective of persistently elevated hCG, however, pregnancy appears to be a viable and safe prospect. Persistently elevated hCG in healthy, nonpregnant women is a rare clinical scenario. Due to the rarity of this condition and potential future malignancy risk, we believe that reporting of future cases is crucial, as is a liaison between national and international trophoblastic disease centers, if we are to gain a more thorough understanding of this possibly premalignant condition.


Perceptual advantage for category-relevant perceptual dimensions: the case of shape and motion.
Category learning facilitates perception along relevant stimulus dimensions, even when tested in a discrimination task that does not require categorization. While this general phenomenon has been demonstrated previously, perceptual facilitation along dimensions has been documented by measuring different specific phenomena in different studies using different kinds of objects. Across several object domains, there is support for acquired distinctiveness, the stretching of a perceptual dimension relevant to learned categories. Studies using faces and studies using simple separable visual dimensions have also found evidence of acquired equivalence, the shrinking of a perceptual dimension irrelevant to learned categories, and categorical perception, the local stretching across the category boundary. These later two effects are rarely observed with complex non-face objects. Failures to find these effects with complex non-face objects may have been because the dimensions tested previously were perceptually integrated. Here we tested effects of category learning with non-face objects categorized along dimensions that have been found to be processed by different areas of the brain, shape and motion. While we replicated acquired distinctiveness, we found no evidence for acquired equivalence or categorical perception.


The Optimal Chinese Herbal Injections for Use With Radiotherapy to Treat Esophageal Cancer: A Systematic Review and Bayesian Network Meta-Analysis.
Ethnopharmacological relevance: Esophageal cancer is one of the most common human cancers, and its incidence is highly endemic in China. The combination of Chinese herbal injections (CHIs) and radiotherapy should be informed by the best available evidence. Aim of the study: To update and expand on previous work in order to compare and rank the efficacy and safety of CHIs in combination with radiotherapy to treat esophageal cancer. Materials and Methods: We searched several electronic databases to identify randomized controlled trials (RCTs) regarding CHIs to treat esophageal cancer from their inception to March 15, 2017. In a network meta-analysis (NMA), the bias of the included trials was assessed by two individuals independently in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. Outcomes such as the clinical effectiveness rate, performance status, adverse reactions (ADRs), and survival rate were evaluated. We performed a random-effects NMA to obtain estimates of efficacy and safety outcomes, and we present these estimates as odds ratios (ORs) and corresponding 95% confidence intervals (CIs) calculated via Stata 13.1 and WinBUGS 1.4 software. Furthermore, the surface under cumulative the ranking curve (SUCRA) was used to rank the efficacy and safety of different CHIs in relation to each outcome. Results: Of 685 identified trials, 55 were eligible for inclusion in the study. These 55 trials included 12 CHIs and 4,114 participants. The cluster analysis results suggested that Compound kushen injection therapy is the optimal CHI treatment for patients with esophageal cancer in terms of improving the clinical effectiveness rate and performance status. Huachansu and Kangai injection are superior in improving 1-year and 2-year survival rates. Lentinan injection may be considered a favorable choice for reliving ADRs, and Compound kushen injection may provide treatment benefits by reducing both gastrointestinal reaction and radiation esophagitis. Conclusions: The current clinical evidence indicated that Compound kushen injection combined with radiotherapy is the most preferable and beneficial option for patients with esophageal cancer in terms of efficacy and safety. However, the results of our study should be interpreted with caution given the limitations of the sample size and the methodological quality of the included trials.


Public health services use in a mountainous area, Vietnam: implications for health for policy.
The aim of this study is to describe the use of public health services in different social and ethnic groups and to explore the implementation of user fee exemption in a mountainous area in Vietnam. A cross-sectional household survey with a structured questionnaire and a four-week diary were used to collect information on illnesses, health seeking behaviour and socioeconomic factors. Three communes in a mountainous district in Northern Vietnam were selected and a random sample of 1,452 individuals in 300 households was drawn. Self-medication was most common (57%) while 30% used public health services when suffering from a health problem. Persons living far from health services attended public health services less frequently than the others (adjusted OR = 0.28; 95% CI 0.15-0.51). This was especially the case for ethnic minorities who were less likely to use public health services than the others were (adjusted OR = 0.47; 95% CI 0.25-0.87). Persons with mild conditions tended to use public health services less than those with more severe conditions (OR = 0.19; 95% CI 0.10-0.37). Health services use was similar among women and men, but the total expenditure per visit was higher for men. Almost no patients supposed to get free attendance had been exempted from user fees. It was found that there was a geographical inequity in use of public health services while there was relatively equal use of these services between social, gender, and ethnic groups. Long distance in combination with failure of the fee exemption may increase inequity in use of health services in remote and isolated areas. These observations contribute to the basis for implementation of the Vietnamese health policy, emphasizing efficiency and equity.


Advances in antibody manufacturing using mammalian cells.
In this review, we describe recent advances in antibody processing technology including: (1) development of proprietary cell lines; (2) improved expression systems optimized by selective technologies to boost underperformers; (3) improved protein-free and serum-free culture media; and (4) attention to glycosylation and other post-translational modifications. Advances in computer technology and sophisticated redesign of bioreactors have been major contributors to the dramatic improvements in antibody yields that have been documented in the last decade. Disposable bioreactor components are now widespread, resulting in improved yields, better quality product and lower costs for producers. Downstream innovations include (1) disposable devices for clarification and purification, (2) improved resins and ligands, and (3) new designs of hardware for improved performance. While there are numerous factors contributing to the increased yields that have been obtained, the most sustained of these is the introduction of disposable technologies on both the upstream and the downstream ends of the process. With the continuing introduction of improved computer technology and technological innovation, there is every reason to believe that quality and quantity of antibody products will continue to improve in the coming years, and supply will be adequate to meet the forthcoming needs of the industry.


Changes in receptor function by oxidative stress in guinea pig tracheal smooth muscle.
We studied the effects of hydrogen peroxide, hypochlorous acid and ozone on muscarinic and beta-adrenergic receptor responses in guinea pig tracheal tissue. Pretreatment of the tracheal strips with hydrogen peroxide (up to 10 mM) did not affect the muscarinic or beta-adrenergic receptor responses after stimulation with methacholine or (-)-isoprenaline respectively. In contrast to hydrogen peroxide, hypochlorous acid (1 mM and 10 mM) decreased the maximal contraction and the pD2-value after stimulation with the muscarinic agonist methacholine. Comparable effects were observed after stimulation with the beta-adrenoceptor agonist (-)-isoprenaline but the beta-adrenoceptor response seemed to be more susceptible to hypochlorous acid treatment than the muscarinic response. In other words, hypochlorous acid changes the balance between muscarinic and beta-adrenergic receptor responses of guinea pig tracheal strips in favour of the muscarinic receptor responses. In vivo exposure of the guinea pigs to 3 ppm ozone for two hours resulted in a hyperreactivity (increase in maximal contraction) after stimulation of the muscarinic receptor with methacholine. No effects were observed in the pD2-value. The beta-adrenergic receptor response was also affected after ozone exposure. No effects were seen in the maximal (-)-isoprenaline induced relaxation but there was an increase (hypersensitivity) in the pD2-value. Our data suggest that oxidative stress modulates receptor responses. Moreover, the type of oxidant seems to differentially affect various receptor responses. This may be of importance to further understand the influence of an oxidative effect (either directly via ozone or through inflammation) in lung tissue.


Best practices for heart failure: a focused review.
Heart failure (HF) is a progressive condition and is associated with high patient mortality rates and frequent hospitalizations. This article provides an overview of clinical, self-management support, and care transitions best practices for HF care in the home care sector. Clinicians armed with competencies in HF management are positioned to meet the 3-part aim of healthcare reform: improved health, better care, and lower cost.


Paraproteinemic neuropathies.
The paraproteinemias are a heterogeneous group of disorders in which monoclonal plasma cells cause the proliferation of monoclonal proteins. They are of importance to clinicians because they often occur in association with neuropathies. Neurologists play a particularly important role when the neuropathy is the presenting feature, in which case they may uncover clinical, laboratory, radiologic, electrodiagnostic, or biopsy findings that lead to identification of the underlying paraproteinemia. The frequency of neuropathies in these patients, and the extent to which such neuropathies dominate the clinical picture, varies significantly between the different paraproteinemias. Treatments may be aimed specifically at the neuropathy, or against the underlying hematologic disorder. In all patients with paraproteinemias, the neurologist can work collaboratively with the hematologist to formulate therapeutic plans and goals and can provide follow-up and monitoring to determine the response of the neuropathy to treatment.


CFD and PTV steady flow investigation in an anatomically accurate abdominal aortic aneurysm.
There is considerable interest in computational and experimental flow investigations within abdominal aortic aneurysms (AAAs). This task stipulates advanced grid generation techniques and cross-validation because of the anatomical complexity. The purpose of this study is to examine the feasibility of velocity measurements by particle tracking velocimetry (PTV) in realistic AAA models. Computed tomography and rapid prototyping were combined to digitize and construct a silicone replica of a patient-specific AAA. Three-dimensional velocity measurements were acquired using PTV under steady averaged resting boundary conditions. Computational fluid dynamics (CFD) simulations were subsequently carried out with identical boundary conditions. The computational grid was created by splitting the luminal volume into manifold and nonmanifold subsections. They were filled with tetrahedral and hexahedral elements, respectively. Grid independency was tested on three successively refined meshes. Velocity differences of about 1% in all three directions existed mainly within the AAA sack. Pressure revealed similar variations, with the sparser mesh predicting larger values. PTV velocity measurements were taken along the abdominal aorta and showed good agreement with the numerical data. The results within the aneurysm neck and sack showed average velocity variations of about 5% of the mean inlet velocity. The corresponding average differences increased for all velocity components downstream the iliac bifurcation to as much as 15%. The two domains differed slightly due to flow-induced forces acting on the silicone model. Velocity quantification through narrow branches was problematic due to decreased signal to noise ratio at the larger local velocities. Computational wall pressure and shear fields are also presented. The agreement between CFD simulations and the PTV experimental data was confirmed by three-dimensional velocity comparisons at several locations within the investigated AAA anatomy indicating the feasibility of this approach.


When to Include a Lumbar Puncture in the Evaluation for Neonatal Sepsis.
Meningitis is a devastating infection in infants and is linked to adverse long-term outcomes. The prevalence of meningitis is variable and depends on gestational age, postnatal age, and clinical setting. Early diagnosis and treatment with appropriate antibiotics are crucial to decrease the risk of morbidity and mortality. Lumbar punctures are essential for the diagnosis of meningitis, but clinicians may defer lumbar puncture if the risk for meningitis is low or if there are substantial concerns regarding the risk associated with the procedure. Awareness of the epidemiology and microbiology of meningitis in infants, as well as valid contraindications to performing a lumbar puncture, is necessary to avoid missed diagnoses and procedure-related adverse effects.


Growth, Morphological, and Physiological Responses to Drought Stress in Bothriochloa ischaemum.
Water shortage in the arid-semiarid regions of China seriously hampers ecosystem construction. Therefore, elucidation of the mechanisms by which vegetation in that area responds to drought stress may enable us to improve utilization of limited water resources and thus contend with the problem of drought and water shortage. We studied Bothriochloa ischaemum, a native grass species, conducted potting control tests to compare several indicators of B. ischaemum grown under three different moisture conditions (80%, 60%, 40% Field capacity represent sufficient water supply, mild water stress, and serious water stress, respectively). Plant response parameters measured included biomass accumulation, root morphology, transient water use efficiency (WUE), stable carbon isotope ratio (δ13C), and stable carbon isotope discrimination (Δ13C) of various plant organs and their interrelationships. B. ischaemum had the greatest WUE under mild drought stress. However, serious drought stress resulted in considerable decline in overall biomass but substantial increase in root-to-shoot ratio and fine-root biomass. Coarse-root biomass dropped appreciably, indicating that serious drought stress leads to allocation non-uniformity of the carbon "sink." δ13C and Δ13C of stem correlated considerably with root morphology, suggesting the feasibility of characterizing WUE, biomass, and root morphology of B. ischaemum via the stable carbon isotope approach. Our evaluation of 21 drought resistance indicators of B. ischaemum showed that under a given moisture treatment gradient one can isolate an optimal indicator to express growth, morphology, and physiology, to improve the accuracy of depicting plant drought resistance and simplify the drought resistance indicator system. This study elucidates the response mechanism of B. ischaemum to drought stress and provides theoretical support to screening of drought-resistant plants across the arid-semiarid regions of China.


Palladium-catalyzed anilide ortho-arylation and subsequent one-pot cyclization to phenanthridines.
The palladium-catalyzed direct arylation of anilides possessing several N-acyl substituents has been demonstrated. Removal of the acyl group by base hydrolysis allows a short and efficient synthesis of 2-aryl or 2,6-diarylanilines. The method is functional group tolerant and allows the presence of chloride and bromide substituents on both the anilide and aryl iodide coupling components. The arylation products can be converted to phenanthridines by the reaction with trifluoroacetic anhydride.


RARER NEED NOT BE BETTER IF COMMONER IS WORSE: FREQUENCY-DEPENDENT SELECTION FOR DEVELOPMENTAL TIME AT THE ALCOHOL DEHYDROGENASE LOCUS OF THE OLIVE FRUIT FLY, BACTROCERA OLEAE.
Whereas the importance of frequency-dependent selection in life-history traits, behavioral characters and source allocation patterns is widely accepted, its role in governing biochemical and molecular polymorphisms remains poorly understood. Here we demonstrate a case of allozyme frequency-dependent selection. When olive fruit flies (Bactrocera oleae) are reared on an artificial larval medium, an allele at the alcohol dehydrogenase locus that is present in very low frequency in natural populations increases to about one-third in less than five generations. We show here that the time from the hatching of the egg to the eclosion of the adult is affected by the genotype composition of the larval population that grows in the same cup of food. Cultures consisting of one genotype only have the longest developmental time, and two-allele cultures in which the two homozygotes and the heterozygote occur in a 1:1:2 ratio show the shortest developmental time. Cultures with intermediate genotypic compositions show intermediate levels of developmental time. The results can be explained by assuming that the developmental time of a genotype depends on the frequency array of all genotypes in the larval population and is not merely a function of its own frequency. It is even possible that the developmental time of a genotype becomes longer as the genotype becomes rarer, yet the genotype will be favored because the developmental times of the competing genotypes become even longer owing to the associated increase of their frequencies. Given that developmental time is inversely related to fitness, this generates a frequency-dependent selection, with developmental times changing progressively until the population arrives at an equilibrium. One optimum population composition that provides a satisfactory fit to allele frequency changes in our experimental populations is when the two alleles occur in equal frequencies and genotypes are in Hardy-Weinberg proportions. We argue that this type of selection is consistent with the role of alcohol dehydrogenase as a detoxifying enzyme in a medium that undergoes continuous chemical changes during its use by the feeding larvae.


B cells and upper airway disease: allergic rhinitis and chronic rhinosinusitis with nasal polyps evaluated.
Introduction: The first mucosal site to encounter inhaled allergen, antigen, and microbes is the upper airway. It must perforce have a rapid system of environmental threat recognition and self-defense. B cells play a critical role in such airway host-defense, tissue surveillance, and immune modulation. Several common upper airway diseases can be defined in the expression of either exaggerated or dysregulated B-cell function within T2-high mucosal inflammatory states.Areas covered: In this review, the authors discuss the immunology of allergic rhinitis (AR) and chronic rhinosinusitis with nasal polyps (CRSwNP) in the context of highlighting key aspects of B-cell biology and function. The review is based on the findings of a literature search using the terms B cells, rhinitis, nasal polyps, and rhinosinusitis.Expert opinion: Despite the emerging role of B-cell overdrive and dysfunction in upper airway disease, studies are lacking specifics to B cells, particularly in association with sinonasal infection and mucosal inflammation. There is a pressing need to focus on how respiratory inflammation, alongside impaired or exaggerated B-cell function, amplifies and further dysregulates immune signaling pathways in the disease setting of AR and CRSwNP.


Sex differences in behavioral and neurochemical profiles after chronic stress: role of housing conditions.
This experiment sought to identify the extent housing conditions can differentially enhance or dampen the effects chronic restraint stress has on exploration and object memory in male and female rats. Subjects were either pair- or singly housed during stress (21 days of 6-h restraint) and maintained under those conditions during poststress behavior testing (7 days). Neurochemical analysis of neural tissue was accomplished by HPLC with electrochemical detection. Interactions between stress and housing conditions were found across both sexes. Stress was associated with less activity in the center of the forced open-field in both sexes. Stress also decreased the latency for males to enter the free open-field to female levels. Object recognition was greatly impaired in double-housed males but unaffected by stress or housing in females. Object location memory was impaired in stressed males if they were singly housed, and females performed as well as control males only if they were stressed. Both sexes generally showed increased in hippocampal (CA3) norepinephrine levels in their respective stress groups. Singly housed subjects had higher CA1 serotonin levels compared to double-housed subjects, whereas in the prefrontal cortex, a general sex difference was found with females having higher levels of serotonin and dopamine metabolites. These results show that stress affects limbic neurochemistry across sex, although only males exhibit stress-dependent decrements in object memory. Housing condition also has a profound effect on neurochemistry and male performance on object recognition. Thus, housing condition is a critical variable for male models of stress that can influence the extent the stress manipulation affects behavior. The differences observed across sex are further discussed in the context of behavioral inhibition.


The 3D structure of the apical complex and association with the flagellar apparatus revealed by serial TEM tomography in Psammosa pacifica, a distant relative of the Apicomplexa.
The apical complex is one of the defining features of apicomplexan parasites, including the malaria parasite Plasmodium, where it mediates host penetration and invasion. The apical complex is also known in a few related lineages, including several non-parasitic heterotrophs, where it mediates feeding behaviour. The origin of the apical complex is unclear, and one reason for this is that in apicomplexans it exists in only part of the life cycle, and never simultaneously with other major cytoskeletal structures like flagella and basal bodies. Here, we used conventional TEM and serial TEM tomography to reconstruct the three dimensional structure of the apical complex in Psammosa pacifica, a predatory relative of apicomplexans and dinoflagellates that retains the archetype apical complex and the flagellar apparatus simultaneously. The P. pacifica apical complex is associated with the gullet and consists of the pseudoconoid, micronemes, and electron dense vesicles. The pseudoconoid is a convex sheet consisting of eight short microtubules, plus a band made up of microtubules that originate from the flagellar apparatus. The flagellar apparatus consists of three microtubular roots. One of the microtubular roots attached to the posterior basal body is connected to bypassing microtubular strands, which are themselves connected to the extension of the pseudoconoid. These complex connections where the apical complex is an extension of the flagellar apparatus, reflect the ancestral state of both, dating back to the common ancestor of apicaomplexans and dinoflagellates.


Majorana fermions and non-Abelian statistics in three dimensions.
We show that three dimensional superconductors, described within a Bogoliubov-de Gennes framework, can have zero energy bound states associated with pointlike topological defects. The Majorana fermions associated with these modes have non-Abelian exchange statistics, despite the fact that the braid group is trivial in three dimensions. This can occur because the defects are associated with an orientation that can undergo topologically nontrivial rotations. A feature of three dimensional systems is that there are "braidless" operations in which it is possible to manipulate the ground state associated with a set of defects without moving or measuring them. To illustrate these effects, we analyze specific architectures involving topological insulators and superconductors.


Education for Community-based Family Medicine: A Social Need in the Real World.
One of the most critical social problems in Japan is the remarkable increase in the aging population. Elderly patients with a variety of complications and issues other than biomedical problems such as dementia and life support with nursing care have been also increasing. Ever since the Japanese economy started to decline after the economic bubble burst of 1991 and the Lehman Brothers bankruptcy in 2008, how we can resolve health problems of the elderly at a lower cost has become one of our most challenging social issues. On the other hand, the appropriate supply of medical and welfare resources is also a fundamental problem. The disparity of physician distribution leads to a marked lack of medical services especially in remote and rural areas of Japan. The government has been attempting to recruit physicians into rural areas through a regional quota system. Based on this background, the medical field pays a great amount of attention to community-based family medicine (CBFM). CBFM requires basic knowledge of community health and family medicine. The main people involved in CBFM are expected to be a new type of general practitioner that cares for residents in targeted communities. To improve the performance of CBFM doctors, we need to establish a better CBFM education system and assess it appropriately when needed. Here, we review the background of CBFM development and propose an effective education system.


The Efficacy of 2% Topical Rebamipide on Conjunctival Squamous Metaplasia and Goblet Cell Density in Dry Eye Disease.
Purpose: To clarify the pharmacological effects of 2% rebamipide eye drops on mucosal membrane functions of the ocular surface epithelium, we investigated keratoconjunctival alterations at the cellular level in this study. Methods: Fifteen patients with definite dry eye disease were recruited from outpatient clinics of the Department of Ophthalmology, Ichikawa General Hospital. The patients received treatment with 2% rebamipide eye drops q.i.d for 12 weeks. Symptom score assessment, tear film breakup time, fluorescein and lissamine green ocular surface vital staining, grading of lid wiper epitheliopathy, Cochet-Bonnet corneal sensitivity, assessment of squamous metaplasia grades, and goblet cell density calculations from conjunctival impression cytology samples, as well as evaluation of nucleocytoplasmic ratios and corneal epithelial cells from in vivo confocal microscopy images before and 3 months after treatment were performed. Results: The mean symptom scores, tear film breakup time values, ocular surface fluorescein and lissamine green vital staining scores, and lid wiper scores showed a significant improvement after treatment (P < 0.01). The mean squamous metaplasia grade also showed a significant improvement (1.2 ± 0.1 → 0.3 ± 0.1) 3 months after treatment (P = 0.004). There were similar significant improvements in the mean corneal epithelial cell density (660.1 ± 62.6 → 1015.5 ± 43.5 cells/mm2) (P = 0.002) and nucleocytoplasmic ratios (0.1 ± 0.0 → 0.2 ± 0.0) (P = 0.0042) after treatment. Conclusions: Topical use of 2% rebamipide for 3 months was associated with improvements in ocular surface differentiation due to changes of mucosal functions at the cellular level. These alterations may explain objective and subjective improvements in dry eye disease.


Biological responses of ligament fibroblasts and gene expression profiling on micropatterned silicone substrates subjected to mechanical stimuli.
In this study, ligament fibroblasts were cultivated on micropatterned silicone substrates and subjected to cyclic stretching to simulate the in vivo biomechanical environment during ligament healing. Without stretching, ligament fibroblasts were aligned parallel to the microgrooves on the silicone substrate surface. However, we previously reported that uniaxial cyclic stretching induces alignment perpendicular to the stretching axis. With stretching on a microgrooved surface, cell proliferation and collagen production were greatly enhanced. The exact functions of the micropatterned surface and mechanical stimuli are unknown. Therefore, in gene expression microarray experiments, genes whose expression is inhibited by subculture from passage 0 (P0) to passage 8 (P8) and enhanced by micropatterning and stretching were sought out. The following six genes were selected: MGP, GADD45A, UNC5B, TGFB1, COL4A1, and COL4A2. The selected genes play fundamental roles in cell proliferation, differentiation, apoptosis, and structural maintenance. On the basis of the obtained gene expression profiles, we identified candidate genes that might be involved in responses to a micropatterned surface and mechanical stretching.


COMMITTED EFFECTIVE DOSE DUE TO THE INTAKE OF 40K, 226Ra, 228Ra AND 228Th CONTAINED IN FOODS INCLUDED IN THE DIET OF THE RIO DE JANEIRO CITY POPULATION, BRAZIL.
Annual effective dose due to the consumption of 40K, 226Ra, 228Ra and 228Th was estimated from high-resolution gamma spectrometry, food consumption data for the inhabitants of Rio de Janeiro City and dose coefficients published by the ICRP 119. A total of 31 samples of cereals, grains, vegetables, flours, liquid and perishables were analyzed. 40K was measured in all samples, and bean sample presented highest specific concentration 489.36 ± 23.70 Bq kg-1. The highest specific concentration for 226Ra, 228Ra and 228Th was measured in pumpkin (7.82 ± 1.09 Bq kg-1), carrot (30.18 ± 1.99 Bq kg-1) and beet (2.43 ± 0.48 Bq kg-1), respectively. The highest contribution to annual effective dose came from beans (556.3 μSv), potato (12.5 μSv), carrot (10.3 μSv), banana (4.7 μSv) and beet (3.3 μSv). It was observed that updates of daily food consumption values was the main reason for an up to 10-fold difference between the annual effective dose found in the present study and literature data.


A practical statistical quality control scheme for the industrial hygiene chemistry laboratory.
A computerized statistical quality control system has been developed for use in the industrial hygiene chemistry laboratory. The system is practical and sufficiently flexible to allow for multiple analytes, concentrations, replicate sizes and sample types. The computerized system provides an immediate evaluation of the quality of analytical results and produces automatically simple but informative accuracy and precision quality control charts.


Fluorescence intensity- and lifetime-based glucose sensing using glucose/galactose-binding protein.
We review progress in our laboratories toward developing in vivo glucose sensors for diabetes that are based on fluorescence labeling of glucose/galactose-binding protein. Measurement strategies have included both monitoring glucose-induced changes in fluorescence resonance energy transfer and labeling with the environmentally sensitive fluorophore, badan. Measuring fluorescence lifetime rather than intensity has particular potential advantages for in vivo sensing. A prototype fiber-optic-based glucose sensor using this technology is being tested.


Proteomic Analysis of Secretomes of Oncolytic Herpes Simplex Virus-Infected Squamous Cell Carcinoma Cells.
Oncolytic herpes simplex virus type 1 (HSV-1) strain RH2 induced immunogenic cell death (ICD) with the release and surface exposure of damage-associated molecular patterns (DAMPs) in squamous cell carcinoma (SCC) SCCVII cells. The supernatants of RH2-infected SCCVII cells also exhibited antitumor ability by intratumoral administration in SCCVII tumor-bearing mice. The supernatants of RH2-infected cells and mock-infected cells were concentrated to produce Med24 and MedC for proteomic analyses. In Med24, the up- and down-regulated proteins were observed. Proteins including filamin, tubulin, t-complex protein 1 (TCP-1), and heat shock proteins (HSPs), were up-regulated, while extracellular matrix (ECM) proteins were markedly down-regulated. Viral proteins were detected in Med 24. These results indicate that HSV-1 RH2 infection increases the release of danger signal proteins and viral gene products, but decreases the release of ECM components. These changes may alter the tumor microenvironment (TME) and contribute to enhancement of anti-tumor immunity against SCC.


Highly Defective Dark Nano Titanium Dioxide: Preparation via Pulsed Laser Ablation and Application.
The development of methods to synthesize and study the properties of dark titania is of the utmost interest due to prospects for its use, primarily in photocatalysis when excited by visible light. In this work, the dark titania powder was prepared by pulsed laser ablation (Nd:YAG laser, 1064 nm, 7 ns) in water and dried in air. To study the changes occurring in the material, the thermal treatment was applied. The structure, composition, and properties of the obtained powders were studied using transmission electron microscopy, low-temperature N2 adsorption/desorption, X-ray diffraction, thermogravimetry/differential scanning calorimetry, X-ray photoelectron, Raman and UV-vis spectroscopies, and photoluminescence methods. The processes occurring in the initial material upon heating were studied. The electronic structure of the semiconductor materials was investigated, and the nature of the defects providing the visible light absorption was revealed. The photocatalytic and antibacterial activities of the materials obtained were also studied. Dark titania obtained via laser ablation in liquid was found to exhibit catalytic activity in the phenol photodegradation process under visible light (> 420 nm) and showed antibacterial activity against Staphylococcus aureus and bacteriostatic effect towards Escherichia coli.


Associations Between Gut Microbiota and Asthma Endotypes: A Cross-Sectional Study in South China Based on Patients with Newly Diagnosed Asthma.
This study aimed to investigate the gut microbiome profile in different inflammatory phenotypes of treatment-naive newly diagnosed asthmatic adults, to gain insight on the associations between intestinal microbiota and phenotypic features that characterize asthma heterogeneity to develop new treatments for asthma. Fresh stool samples were obtained from 20 healthy subjects and 47 newly diagnosed asthmatic patients prior to any interventions. The asthmatics were divided into allergic and non-allergic cohorts. Intestinal microbiota was analyzed by 16S rRNA next-generation sequencing. Demographic and clinical parameters were collected. Alpha and beta diversity analysis were calculated to detect differences within sample phylotype richness and evenness between controls and asthmatic patients. Statistically significant differences between samples were analyzed for all used metrics, and features of gut bacterial community structure were evaluated in relation to extensive clinical characteristics of asthmatic patients. Gut microbial compositions were significantly different between asthmatic and healthy groups. Alpha-diversity of the gut microbiome was significantly lower in asthmatics than in controls. The microbiome between allergic and non-allergic asthmatic patients were also different, and 28 differential species were identified. PPAR signaling pathway, carotenoid biosynthesis, and flavonoid biosynthesis were significantly positively correlated with allergy-associated clinical index, including FENO value, blood eosinophil counts, and serum IgE and IL-4 levels. A combination of Ruminococcus bromii, Brevundimonas vesicularis, and Clostridium disporicum showed an AUC of 0.743 in the specific allergic/non-allergic cohort. When integrating C. disporicum, flavone, flavonol biosynthesis, and serum IL-4 values, the AUC achieved 0.929 to classify asthmatics. At the same time, C. colinum and its associated functional pathway exhibited an AUC of 0.78 to distinguish allergic asthmatics from those without allergies. We demonstrated a distinct taxonomic composition of gut microbiota in different asthmatic phenotypes, highlighting their significant relationships. Our study may support considerations of intestinal microbial signatures in delineating asthma phenotypes.


Reactivity and binding energies of transition metal halide ions with benzene.
We have generated novel halogen-ligated transition metal ions MX(n)+ (M = Sc, Ti, V, and Fe, X = Cl, Br and I, n = 1-3). We have explored their reactions with benzene, a typical aromatic hydrocarbon. Attachment of one benzene molecule is usually rapid, whereas attachment of a second benzene molecule is generally much slower. The kinetics were analyzed to estimate binding energies, modeling the attachment reaction as a radiative association process. In all cases the Standard Hydrocarbon semiquantitative estimation approach was employed, and in some cases the more accurate variational transition state (VTST) kinetic modeling approach was also applied. Density functional (DFT) quantum calculations were also performed to give computed binding energies for some of the complexes. Taking previously determined binding energies for halogen-ligated alkaline-earth ions as benchmarks, it is concluded that binding of the first benzene molecule to the transition-metal species is strongly enhanced by specific chemical interactions, while binding of the second benzene molecule is more nearly electrostatic. The binding energies are not strongly dependent on the identity of the transition metal ion, and the metal-ion dependences can be rationalized in terms of valence-orbital occupations of the metals. The binding energies are nearly independent of the identity of the halogen ligands.


A Novel Technique Debulking Vegetations in Tricuspid Endocarditis and Venacava Utilizing AngioVac Aspiration System.
The AngioVac system (AngioDynamics Inc., Latham, NY) is used for the removal of commonly encountered intravascular material, such as thrombus or vegetations in the right atrium, right ventricle, superior vena cava, and inferior vena cava. Patients with high surgical risk having tricuspid endocarditis and superior vena cava thrombus can be treated with the AngioVac system, hence mitigating the risks for this patient population. We present a case series with the utilization of the AngioVac device to reduce the vegetation size and decrease the risk of emboli with effective antibiotic penetration. Transesophageal echocardiography shows a reduction in the size of the vegetations in all three cases with no postoperative complications. This case series demonstrates a novel technique debulking vegetations in tricuspid endocarditis and vena cava.


Additive and reducing Effects between Calcium Hydroxide and Current Irrigation Solutions.
Microorganisms should be considered to have the major role in starting and perpetuation of pulpo-periapical diseases. Using intracanal medicaments is necessary to gain a bacteria-free environment in the canal system. Calcium hydroxide (abbreviated as Ca(OH)2), which is the most commonly used medicament in endodontic therapy, has been shown to be effective against primary sources of infection; however, its effectiveness against some microorganisms, such as Candida albicans and Enterococcus faecalis has not been proved. On the other hand, sodium hypochlorite (NaOCl), chlorhexidine (CHX), and iodine potassium iodide (IKI) have been shown to be the potent medicaments against these microorganisms. Because of this fact, combination of Ca(OH)2 and some irrigants of the root canal has been suggested as potential intracanal medicaments. The aim of this literature review is to identify and address the efficacy of Ca(OH)2 in combined with some of these irrigating solutions.


Lepidic predominant adenocarcinoma and invasive mucinous adenocarcinoma of the lung exhibit specific mucin expression in relation with oncogenic drivers.
To evaluate MUC1, MUC2, MUC5B, MUC5AC, and MUC6 expression in invasive lepidic predominant adenocarcinoma (LPA) and invasive mucinous adenocarcinoma (IMA) of the lung, and the impact of oncogenic drivers. MUC1, MUC2, MUC5B, MUC5AC, MUC6, TTF1 and Hnf4α immunohistochemistry was performed on surgical samples from 52 patients with IMA (n=25) or LPA (n=27). We searched for EGFR, KRAS, BRAF, and HER2 mutations and ALK, ROS1, and NRG1 rearrangements. MUC1, MUC2, MUC5B, MUC5AC, and MUC6 expression was detected in tumor cells in 77%, 2%, 63%, 36%, and 21% of cases, respectively. MUC1 was significantly more overexpressed in LPA. MUC5B, MUC5AC, and MUC6 were typically detected in goblet cells and overexpressed in IMA. Hnf4α-positive IMA (n=11) were TTF1-negative and typically did not expressed MUC1 and expressed MUC5AC and MUC6. Hnf4α-negative IMA (n=14) showed a reverse profile of mucins expression, with MUC1 expression and a lack of MUC5AC and MUC6 expression. EGFR-positive status was significantly associated with LPA, MUC1 expression, and no MUC5B, MUC5AC, or MUC6 expression. KRAS-positive status was significantly associated with IMA and MUC5B and MUC5AC expression. LPA and IMA exhibit specific mucin expression profiles, with MUC1 being associated with LPA, while MUC5B, MUC5AC, and MUC6 were associated with IMA. Hnf4α expression and EGFR and KRAS mutations may play a role in mucin expression profiles of these lung adenocarcinoma subtypes.


Transverse and longitudinal osteotomy for the treatment of macrodactyly simplex congenita - a case report.
We report on a three-year-old girl with a severely enlarged right ring finger, which was diagnosed as macrodactyly simplex congenita. This was treated by epiphysial resection and osteosynthesis of the distal interphalangeal joint, longitudinal and transverse osteotomy of the phalanges, and soft tissue coverage using palmar proximal and dorsal distal flaps taken from the original oversised finger.


Ventilatory response to brief arousal from non-rapid eye movement sleep is greater in men than in women.
Sleep apnea syndromes are more common in men than in women. The ventilatory response to arousal from sleep may be an important determinant of respiratory stability/instability and could contribute to this sex difference. We therefore compared changes in ventilation, end-tidal carbon dioxide (CO2), upper airway resistance, heart rate, and finger photoplethysmogram pulse wave amplitude after both spontaneous and tone-induced arousal from non-rapid eye movement sleep in 13 men and 13 women. At sleep onset, ventilation fell and both upper airway resistance and end-tidal CO2 rose, but these changes were not different between sexes. Spontaneous arousal (duration, 6.6 +/- 0.2 seconds) resulted in a biphasic ventilatory response consisting of brief hyperventilation (5 seconds) followed by prolonged hypoventilation (30-40 seconds) on resumption of sleep. The biphasic ventilatory response was greater in men than in women and did not appear to be explained by different wake-to-sleep increments in end-tidal CO2 or upper airway resistance between sexes. Peripheral vasoconstriction with arousal was also greater in men than in women. Ventilatory responses were more marked after tone-induced versus spontaneous arousals and when subjects slept supine compared with the left lateral position. These results suggest that male sex and supine position are associated with greater ventilatory instability after arousal from sleep.


RNAspa: a shortest path approach for comparative prediction of the secondary structure of ncRNA molecules.
In recent years, RNA molecules that are not translated into proteins (ncRNAs) have drawn a great deal of attention, as they were shown to be involved in many cellular functions. One of the most important computational problems regarding ncRNA is to predict the secondary structure of a molecule from its sequence. In particular, we attempted to predict the secondary structure for a set of unaligned ncRNA molecules that are taken from the same family, and thus presumably have a similar structure. We developed the RNAspa program, which comparatively predicts the secondary structure for a set of ncRNA molecules in linear time in the number of molecules. We observed that in a list of several hundred suboptimal minimal free energy (MFE) predictions, as provided by the RNAsubopt program of the Vienna package, it is likely that at least one suggested structure would be similar to the true, correct one. The suboptimal solutions of each molecule are represented as a layer of vertices in a graph. The shortest path in this graph is the basis for structural predictions for the molecule. We also show that RNA secondary structures can be compared very rapidly by a simple string Edit-Distance algorithm with a minimal loss of accuracy. We show that this approach allows us to more deeply explore the suboptimal structure space. The algorithm was tested on three datasets which include several ncRNA families taken from the Rfam database. These datasets allowed for comparison of the algorithm with other methods. In these tests, RNAspa performed better than four other programs.


Epicardial and subcutaneous adipose tissue Fatty acids profiles in diabetic and non-diabetic patients candidate for coronary artery bypass graft.
We have recently shown that in high cholesterol-fed rabbits, the sensitivity of epicardial adipose tissue to changes in dietary fat is higher than that of subcutaneous adipose tissue. Although the effects of diabetes on epicardial adipose tissue thickness have been studied, the influence of diabetes on profile of epicardial free fatty acids (FFAs) has not been studied. The aim of this study is to investigate the effect of diabetes on the FFAs composition in serum and in the subcutaneous and epicardial adipose tissues in patients undergoing coronary artery bypass graft (CABG). Forty non-diabetic and twenty eight diabetic patients candidate for CABG with >75% stenosis participated in this study. Fasting blood sugar (FBS) and lipid profiles were assayed by auto analyzer. Phospholipids and non-estrified FFA of serum and the fatty acids profile of epicardial and subcutaneous adipose tissues were determined using gas chromatography method. In the phospholipid fraction of diabetic patients' serum, the percentage of 16:0, 18:3n-9, 18:2n-6 and monounsaturated fatty acids (MUFAs) was lower than the corresponding values of the non-diabetics; whereas, 18:0 value was higher. A 100% increase in the amount of 18:0 and 35% decrease in the level of 18:1n-11 was observed in the diabetic patients' subcutaneous adipose tissue. In epicardial adipose tissue, the increase of 18:0 and conjugated linolenic acid (CLA) and decrease of 18:1n-11, w3 (20:5n-3) and 22:6n-3 were significant; but, the contents of arachidonic acid and its precursor linoleic acid were not affected by diabetes. The fatty acids' profile of epicardial and subcutaneous adipose tissues is not equally affected by diabetes. The significant decrease of 16:0 and w3 fatty acids and increase of trans and conjugated fatty acids in epicardial adipose tissue in the diabetic patients may worsen the formation of atheroma in the related arteries.


Chiral assembly of weakly curled hard rods: Effect of steric chirality and polarity.
We theoretically investigate the pitch of lyotropic cholesteric phases composed of slender rods with steric chirality transmitted via a weak helical deformation of the backbone. In this limit, the model is amenable to analytical treatment within Onsager theory and a closed expression for the pitch versus concentration and helical shape can be derived. Within the same framework, we also briefly review the possibility of alternative types of chiral order, such as twist-bend or screw-like nematic phases, finding that cholesteric order dominates for weakly helical distortions. While long-ranged or "soft" chiral forces usually lead to a pitch decreasing linearly with concentration, steric chirality leads to a much steeper decrease of quadratic nature. This reveals a subtle link between the range of chiral intermolecular interaction and the pitch sensitivity with concentration. A much richer dependence on the thermodynamic state is revealed for polar helices where parallel and anti-parallel pair alignments along the local director are no longer equivalent. It is found that weak temperature variations may lead to dramatic changes in the pitch, despite the lyotropic nature of the assembly.


Trends in Hospital Admissions for Systolic and Diastolic Heart Failure in the United States Between 2004 and 2017.
Heart failure (HF) affects 6 million people in the United States and costs $30 billion annually. It is unclear whether improvements in length of stay and mortality over the last few decades hold true for both systolic and diastolic HF. To better assess the epidemiological and economic burden of HF, we assessed the trends in outcomes and costs for both systolic and diastolic HF. We identified hospitalizations for systolic and diastolic HF in the National Inpatient Sample database and evaluated trends over the period from 2004 to 2017, adjusting for demographics and co-morbidities. The proportion of patients admitted with an exacerbation of systolic HF increased from 42% to 63% over the study period. We found an overall decreasing trend between 2004 and 2011 in the length of stay for HF in general with a sharper decrease in diastolic than systolic HF. Inpatient mortality decreased between 2004 and 2007 and stabilized between 2008 and 2016. Systolic HF was associated with higher mortality than diastolic HF. The total inflation-adjusted cost did not change significantly over the study period, with systolic HF costing, on average, $3,036 more than diastolic HF per admission. In conclusion, systolic HF overtook diastolic HF, accounting for most HF hospitalizations in 2008. The higher hospitalization costs for systolic HF relative to diastolic HF may have resulted, in part, from greater use of advanced support devices in patients with systolic HF.


Neurotrophins and Proneurotrophins: Focus on Synaptic Activity and Plasticity in the Brain.
Neurotrophins have been intensively studied and have multiple roles in the brain. Neurotrophins are first synthetized as proneurotrophins and then cleaved intracellularly and extracellularly. Increasing evidences demonstrate that proneurotrophins and mature neurotrophins exerts opposing role in the central nervous system. In the present review, we explore the role of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4) and their respective proform in cellular processes related to learning and memory. We focused on their roles in synaptic activity and plasticity in the brain with an emphasis on long-term potentiation, long-term depression, and basal synaptic transmission in the hippocampus and the temporal lobe area. We also discuss new findings on the role of the Val66Met polymorphism on the BDNF propeptide on synaptic activity.


Testing a novel multicomponent intervention to reduce meat consumption in young men.
Both epidemiological studies and randomised controlled trials have shown that meat-eating can be harmful to human health. Meat-eating is also considered to be a moral issue, impacting negatively on the environment and the welfare of animals. To date, very little scientific research has aimed to reduce this dietary behavior. Therefore, the current research tests the effectiveness of a 4-week multicomponent intervention designed to reduce meat-eating. Using a randomised controlled trial procedure, thirty-two young men (mean age: 23.5 ± 3.1 years old) were randomly assigned into two equal groups, the intervention vs control group. Based on research in social and health psychology, the intervention was composed of five components expected to reduce meat consumption: a social norm component; an informational/educational component; an appeal to fear; a mind attribution induction; and a goal setting/self-monitoring component. Measures of different types of meat intake (using dietary journals) were taken at baseline (Time 1) as well as 2 (Time 2) and 4 weeks later (Time 3). Emotions and attitudes toward meat-eating and animals were also assessed at Time 3. Significant reductions in total and weekend red meat consumption as well as cold cuts consumed on the weekend were observed in the intervention condition from Time 1 to Time 3. Moreover, reduced positive emotions toward eating meat mediated the reduction in red meat consumption. The component of the intervention that participants most often perceived as having led to a reduction in their meat consumption was the informational component. In conclusion, results provide support for the effectiveness of the multicomponent intervention and for the mediating role of positive emotions when predicting behavioral changes in meat consumption.


Helping young adults understand their learning disabilities.
This study evaluated the effectiveness of an Understanding Learning Disabilities (ULD) course designed to promote self-understanding and self-advocacy skills in young adults with learning disabilities (LD) functioning in the low-average range intellectually. Nineteen first-year students with LD at the Threshold Program at Lesley College received 15 hours of training throughout one semester. Seventeen first-year students with LD at the Para-Educator Center at New York University served as the control group. Both a paper-and-pencil questionnaire and a role-play interview were used as pre- and postassessments. Results of ANOVAs performed on posttest questionnaire and interview scores support the effectiveness of the ULD course in expanding students' knowledge base regarding their learning disabilities and teaching them to apply their self-understanding in a social context. Moreover, students' performance on the questionnaire was an effective predictor of future work adjustment 1 year later. Significant correlates of ULD performance include IQ, academic achievement, and vocational functioning.


Serological evidence of rickettsial infections in Delhi.
Rickettsial infections remain under-diagnosed due to lack of diagnostic facilities in developing world. Here we present our experience at National Centre for Disease Control, Delhi, about a serosurvey done in Delhi for rickettsial disease with easy to perform low cost, low expertise Weil Felix test. On the basis of cut-off titre obtained in healthy population, Weil Felix test results were interpreted along with clinical data. Entomological investigation was also carried out in select areas of Delhi. Rodents were trapped from houses and gardens and vector mites were collected. When serum samples were collected during initial 5 yr period from patients with fever of unknown origin, seropositivity was 8.2 per cent whereas when rickettsial infection was kept as one of the differential diagnosis by clinicians seropositivity increased to 33.3 per cent. Rickettsial infections detected were scrub typhus (48.2%) followed by spotted fever group (27.5%) and typhus group (6.8%) during 2005-2009. In preliminary entomological survey vector mite Leptotombidium deliense was found on rodents. Our findings showed that results of Weil Felix test should not be disregarded, rather clinically compatible cases should be treated to save lives.


[Alleged suicide by insulin].
A 26-year-old man, who was on probation, was found dead in his home by his mother. Insulin vials and 2 insulin pens, which the man's stepfather (an insulin-dependent diabetic) had been missing for over a week, were found next to the deceased. The circumstances suggested suicide by an injected insulin overdose. At the time of the autopsy, the corpse showed already marked signs of autolysis. Clinical chemical tests confirmed the injection of insulin, but indicated hyperglycemia at the time of death. Toxicological analyses revealed that the man had consumed amphetamine, cannabinoids, and tramadol in the recent past. Histological examination finally revealed extensive bronchopneumonia as the cause of death. The most plausible explanation for the results of the autopsy and the additional examinations was an injection of insulin as a failed attempt of self-treatment. It is conceivable that the man had discovered by a rapid test that he was a diabetic, but had decided not to go to a doctor to avoid disclosure of parole violation due to continued drug abuse. He may have misinterpreted the symptoms caused by his worsening bronchitis and the developing bronchopneumonia as symptoms of a diabetic metabolic status and may have felt compelled to treat himself with insulin.